Dimethyl titanocene is an effective methylenating reagent for a variety of carbonyl compounds, including esters and lactones (N. A. Petasis and E. I. Bzowej, J. Am. Chem. Soc., 112, 6392-6394 (1990)). The reagent has been used to methylenate heteroatom-substituted carbonyls, and is also a ring-opening metathesis polymerization catalyst (N. A. Petasis and S.-P. Lu, Tetrahedron Lett., 36, 2393 (1995); N. A. Petasis and D.-K. Fu, J. Am. Chem. Soc., 115, 7208 (1993)). Accordingly, it is well recognized in the art that dimethyl titanocene has become a valuable synthetic tool. See for example the extensive use of dituethyl titanocene by e.g., N. A. Petasis and M. A. Patane, Tetrahedron Lett., 31, 6799 (1990); P. DeShong and P. J. Rybczynski, J. Org. Chem., 56, 3207 (1991); J. S. Swenton, D. Bradin, B. D. Gates, J. Org. Chem., 56, 6156 (1991); N. A. Petasis and E. I. Bzowej, Tetrahedron Lett., 34, 1721 (1993); H. K. Chenault and L. F. Chafin, J. Org. Chem., 59, 6167 (1994); D. Kuzmich, S. C. Wu, D.-C. Ha, C.-S. Lee, S. Ramesh, S. Atarashi, J.-K. Choi and D. J. Hart, J Am. Chem. Soc., 116, 6943 (1994); U.S. Pat. No. 5,087,790 (1992); and C. Dorn, et al., PCT Patent Publication WO 95/16679 (1995).
Although synthetic methodology may require the availablity of this reagent on a multi-kilogram scale, the published preparation procedure for the preparation of dimethyl titanocene is not amenable to large scale operations (K. Claus and H. Bestian, Justus Liebigs Ann. Chem., 654, 8 (1962)). The reference protocol calls for methylating titanocene dichloride with the pyrophoric reagent methyl lithium in ether, followed by an aqueous quench, and then a work-up where the material was isolated as a solid. However, it has been noted that Cp.sub.2 Ti(CH.sub.3).sub.2 is unstable in the solid phase, and evaporation of solutions containing the reagent have decomposed unpredictably (for a discussion of the solid state stability of dimethyl titanocene see: G. J. Erskine, J. Hartgerink, E. L. Weinberg and J. D. McCowan J. Organomet. Chem., 170, 51 (1979) and references cited therein). The preparation of dimethyl titanocene from methylmagnesium iodide and dichlorotitanocene in diethyl ether has been reported in German Patent Publication No. 1,037,446 (1959) to Farbwerke Hoechst, however, few details of the procedure are provided, and a yield of only 58% is reported.
Accordingly, there is a need in the art for a safer and more economical method for the preparation of dimethyl titanocene. The present invention provides a safer method for the preparation of dimethyl titanocene in high yield from titanocene dichloride and methyl magnesium chloride. The present process avoids the use of methyl lithium which is a pyrophoric reagent and hazardous to use on a large scale. Methylmagnesium chloride is safer to use than methyllithium and is also less expensive.